Department of Histology, Medical University of Gdansk, Poland.
J Physiol Pharmacol. 2009 Oct;60 Suppl 4:71-5.
Although there is a convincing evidence supporting an important role for microorganisms in the pathogenesis of Inflammatory Bowel Disease (IBD) which comprises ulcerative colitis (UC) and Crohn's disease (CD), the specific mechanisms involved remain unclear. Toll-like receptors (TLR) recognize various molecules of microbiota including flagellin, the principal protein of motile comensal and pathogenic bacteria implicated in the pathogenesis of IBD.
To investigate the expression of the TLR-5 receptors at the mRNA and protein levels in the mucosa of UC patients.
TLR-5 mRNA was quantified by the validated real-time PCR (QPCR) in mucosal biopsies of 99 UC patients and 34 control patients and TLR-5 protein was detected by immunohistochemistry (IHC) in 57 UC and 10 control patients.
Significantly decreased TLR-5 gene expression at mRNA and protein level was found in the mucosa of patients with moderate and severe disease activity as compared to patients with low UC activity and control. TLR-5 immunoreactivity was found in the mucosa of UC patients and normal controls in the cytoplasm of enterocytes and at their basolateral domain. However, the intensity of the IHC reaction in specimens from UC patients was substantially lower than in control samples.
The decreased expression of TLR-5 gene and protein in the mucosa of UC patients suggests that down-regulation of TLR-5 is probably caused by the increased number of ligand molecules in the proximity of epithelial cells in the inflamed tissue.
尽管有令人信服的证据表明微生物在炎症性肠病（IBD）的发病机制中起着重要作用，其中包括溃疡性结肠炎（UC）和克罗恩病（CD），但涉及的具体机制仍不清楚。Toll 样受体（TLR）识别微生物的各种分子，包括鞭毛蛋白，这是运动共生菌和致病性细菌的主要蛋白，与 IBD 的发病机制有关。
研究 TLR-5 受体在 UC 患者黏膜中的 mRNA 和蛋白水平的表达。
通过验证的实时 PCR（QPCR）定量测定 99 例 UC 患者和 34 例对照患者的 TLR-5 mRNA，并用免疫组织化学（IHC）检测 57 例 UC 患者和 10 例对照患者的 TLR-5 蛋白。
与 UC 活动度低的患者和对照组相比，中重度疾病活动患者的黏膜 TLR-5 基因表达在 mRNA 和蛋白水平上均显著降低。在 UC 患者和正常对照者的黏膜中均发现 TLR-5 免疫反应原性位于肠上皮细胞的细胞质和基底外侧域。然而，UC 患者标本的 IHC 反应强度明显低于对照标本。
UC 患者黏膜中 TLR-5 基因和蛋白表达的降低表明，TLR-5 的下调可能是由于上皮细胞附近的配体分子数量增加所致。
